Severe Cutaneous Adverse Reactions: The Pharmacogenomics from Research to Clinical Implementation

Int J Mol Sci. 2016 Nov 15;17(11):1890. doi: 10.3390/ijms17111890.

Abstract

Severe cutaneous adverse reactions (SCARs), previously thought to be idiosyncratic or unpredictable, are a deadly form of adverse drug reactions with skin manifestations. Current pharmacogenomic studies of SCARs have made important strides, as the prevention of SCARs, to some extent, appears attainable with the identification of genetic variants for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). Despite the improvement of incidence, a treatment guideline for this devastating condition is still unavailable, highlighting the inadequacy of contemporary accepted therapeutic interventions. As such, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we discuss recent cutting-edge findings concerning the discovery of biomarkers for SCARs and their clinical utilities in the better prediction and early diagnosis of this disease. The knowledge compiled herein provides clues for future investigations on deciphering additional genetic markers for SCARs and the design of clinical trials for the prospective identification of subjects at genetic risk for this condition, ultimately personalizing the medicine.

Keywords: clinical implementation; pharmacogenomics; severe cutaneous adverse reactions.

Publication types

  • Review

MeSH terms

  • Allopurinol / adverse effects
  • Anti-HIV Agents / adverse effects*
  • Anticonvulsants / adverse effects*
  • Biomarkers / metabolism
  • Carbamazepine / adverse effects
  • Dideoxynucleosides / adverse effects
  • Genetic Markers
  • Gout Suppressants / adverse effects*
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology
  • Humans
  • Inactivation, Metabolic / genetics
  • Inactivation, Metabolic / immunology
  • Pharmacogenetics*
  • Precision Medicine
  • Prognosis
  • Safety-Based Drug Withdrawals
  • Stevens-Johnson Syndrome / etiology
  • Stevens-Johnson Syndrome / genetics*
  • Stevens-Johnson Syndrome / immunology
  • Stevens-Johnson Syndrome / pathology

Substances

  • Anti-HIV Agents
  • Anticonvulsants
  • Biomarkers
  • Dideoxynucleosides
  • Genetic Markers
  • Gout Suppressants
  • HLA-B Antigens
  • Carbamazepine
  • Allopurinol
  • abacavir